Urea is often present in waste water but can be used in powering fuel cells and as an alternative oxidation substrate to water in an electrolyser. However, an insufficient mechanistic understanding and the lack of efficient catalysts for the urea oxidation reaction have hampered the development of such applications. Here we demonstrate that a nickel ferrocyanide (Ni2Fe(CN)6) catalyst supported on Ni foam can drive the urea oxidation reaction with a higher activity and better stability than those of conventional Ni-based catalysts. Our experimental and computational data suggest a urea oxidation reaction pathway different from most other Ni-based catalysts that comprise NiOOH derivatives as the catalytically active compound. Ni2Fe(CN)6 appears to be able to directly facilitate a two-stage reaction pathway that involves an intermediate ammonia production (on the Ni site) and its decomposition to N2 (on the Fe site). Owing to the different rate-determining steps with more favourable thermal/kinetic energetics, Ni2Fe(CN)6 achieves a 100 mA cm−2 anodic current density at a potential of 1.35 V (equal to an overpotential of 0.98 V).